The present application relates to biologically effective forms of selenium, and more particularly to monoclinic and amorphous selenium nanoparticles having a size of 1-300 nm; also disclosed are the methods and processes of making such nanoparticles.
Note that the points discussed below may reflect the hindsight gained from the disclosed inventions, and are not necessarily admitted to be prior art.
Selenium is an essential micronutrient for man and animals. The main form of selenium in mammalian is its presence in selenoproteins as selenocysteine (Sec) encoded by the TGA codon in DNA. Sec with its stronger nucleophilicity plays an essential role in some enzyme activities as a key catalytic group. Other biological effects include its anti-oxidative effects.
Selenite and selenate from food and water are used by mammalian cells as selenium sources, and selenite is reduced to selenide by the glutathione-glutaredoxin and the thioredoxin systems, which is used as
However, the toxicity of inorganic selenium compounds, e.g. selenite and selenate, is also well known. It has been a challenge for researchers to develop a food supplement using inorganic selenium compounds.
Reducing selenate and selenite to elemental selenium (Se(0)) by certain fungi and bacteria has been shown to result in detoxification. See Gharieb, M. M., et al. “Reduction of selenium oxyanions by unicellular, polymorphic and filamentous fungi: cellular location of reduced selenium and implications for tolerance,” J. of Industrial Microbiology, 14, 300-31, 1995; and Oremland, R. S., et al., “Structural spectral features of selenium nanospheres produced by Se-respiring bacteria,” Applied and Environmental Microbiology, 70, p 52-60, 2004 (herein after referred to as Oremland).
The detoxicated elemental selenium Se(0) exists both intracellularly and extracelluallarly, some as monoclinic crystals in nanoparticle form (nano-Se) with size around 300 nm. See Oremland. Besides monoclinic selenium, other forms of elemental selenium particles also exist in nature. However, grey and black forms of micrometer size (vitreous, insoluble Se(0) particles) are biologically inert, while the red colloidal selenium nano-particles are biologically effective. See Zhang, J., et al., “Biological effects of a nano red elemental selenium,” BioFactors, 15, page 27-38, 2001 (herein after referred to as Zhang). The entirety of which is hereby incorporated by reference.
It has been shown that the size of elemental selenium nanoparticles plays an important role in their biological activity. For example, as expected, 5-200 nm Nano-Se can directly scavenge free radicals both in vitro and in vivo in a size-dependent fashion. See Peng, D, et al., “(Nano-Se) at supranutritional levels on selenium accumulation and glutathione S-transferase activity,” J. Inorganic Biochem., v. 101, p 1457-1463, October 2007, the entirety of which is hereby incorporated by reference. Because of its bioavailability and higher bioeffects, nano-Se has drawn increasingly greater attention in efforts to develop selenium nutritional supplements and in medical uses.
Although methods to prepare the colloid of amorphous selenium are reported, the produced selenium colloids are unstable, and they easily aggregate together to form micro-sized particles and change into a trigonal crystal form which is not biologically effective.
There is great need to produce stable and well-dispersed selenium nano-particles in monoclinical or colloidal form of biologically effective size for improved biological effects.